PT - JOURNAL ARTICLE AU - Yuki Miyai AU - Daisuke Sugiyama AU - Tetsunari Hase AU - Naoya Asai AU - Tetsuro Taki AU - Kazuki Nishida AU - Takayuki Fukui AU - Toyofumi Fengshi Chen-Yoshikawa AU - Hiroki Kobayashi AU - Shinji Mii AU - Yukihiro Shiraki AU - Yoshinori Hasegawa AU - Hiroyoshi Nishikawa AU - Yuichi Ando AU - Masahide Takahashi AU - Atsushi Enomoto TI - Meflin-positive cancer-associated fibroblasts enhance tumor response to immune checkpoint blockade AID - 10.26508/lsa.202101230 DP - 2022 Jun 01 TA - Life Science Alliance PG - e202101230 VI - 5 IP - 6 4099 - https://www.life-science-alliance.org/content/5/6/e202101230.short 4100 - https://www.life-science-alliance.org/content/5/6/e202101230.full SO - Life Sci. Alliance2022 Jun 01; 5 AB - Cancer-associated fibroblasts (CAFs) are an integral component of the tumor microenvironment (TME). Most CAFs shape the TME toward an immunosuppressive milieu and attenuate the efficacy of immune checkpoint blockade (ICB) therapy. However, the detailed mechanism of how heterogeneous CAFs regulate tumor response to ICB therapy has not been defined. Here, we show that a recently defined CAF subset characterized by the expression of Meflin, a glycosylphosphatidylinositol-anchored protein marker of mesenchymal stromal/stem cells, is associated with survival and favorable therapeutic response to ICB monotherapy in patients with non-small cell lung cancer (NSCLC). The prevalence of Meflin-positive CAFs was positively correlated with CD4-positive T-cell infiltration and vascularization within non-small cell lung cancer tumors. Meflin deficiency and CAF-specific Meflin overexpression resulted in defective and enhanced ICB therapy responses in syngeneic tumors in mice, respectively. These findings suggest the presence of a CAF subset that promotes ICB therapy efficacy, which adds to our understanding of CAF functions and heterogeneity.